This invention relates to solid structures containing active agents such as pharmaceuticals, pesticides, peptides, hormones, enzymes and the like which are adapted for the controlled and prolonged release of the active agent into the surrounding environment. More particularly the invention relates to such solid structures adapted for controllably releasing the active agent(s) contained therein over a prolonged period of time.
The invention further relates to a process for preparing such active agent containing solid structures and as well to a method for providing prolonged release of active agents under controlled conditions of time and concentration.
Numerous attempts have been made to control the mechanism of the release of active agents such as medicaments, hormones, fertilizers, pesticides, trace elements, fragrances and the like so that their release is prolonged i.e., their release takes place over a prolonged period of time.
In the pharmaceutical applications of prolonged release drug forms, the active agent until now has almost always been administered orally in the form of tablets or pills, as liquid solutions or dispersions to be taken orally and as injection solutions or dispersions. In these forms, the medicament is fairly quickly made available in a high concentration. The concentration is over the course of time decreased. The uptake of the active agent which takes place almost always follows an exponential path. From this, it can be easily appreciated that this type of dispensing of active agent provides a thereapeutically significant concentration level for only a short period of time.
Further initially there can be provided a too high drug dosage level so that there exists the danger of an overdose. Later as time passes and the concentration of drug level decreases, there may be insufficient drug available for effective thereapeutic results to be realized.
It can be appreciated that, for most purposes, it is desirable to provide a constant level of active agent and this over a prolonged period.
The same is true in agricultural and forestry fields of application. Fertilizers are mostly used in the form of powders, for example ammonium phosphate powder, and in this form distributed over the planting field, whereby at first a high fertilizer concentration is established. With the first rain, a considerable amount of the salt is washed away or seeps away so that the concentration in the ground is decreased and less of the active agent is available for the plants.
Attempts have been made in order to overcome these previously mentioned disadvantages. For example, the active agent has been introduced in a microporous powder permitting the active agent to be released over a longer period of time.
Also, and particularly in pharmaceutical applications, so-called microcapsules have been employed wherein the active agent is enclosed within a membrane through which it is then diffused. The disadvantage attendant the use of microcapsules lies in that selecting and achieving a desired thickness of the separating partition and required wall strength for obtaining the aimed-for release rate is very difficult. Often the capsules are not totally impervious, or are not strong enough so that when any stress is applied, uncontrolled release of active agent can take place.
It has also been proposed to dispense the active agent in a matrix from which the active agent through diffusion can be discharged into the surrounding environment. The disadvantage of this approach is that the release of the active agent takes place in a graduated fashion and is not possible to arrive at a constant release to be delivered over a prolonged period of time.
In U.S. Pat. Nos. 3,887,699 and 4,011,312 there are described similar or analogous methods for achieving prolonged release of active agents. The patents describe methods of dispensing an active agent in a polymeric material, so that the active material will be diffused from the surface layer of the polymer.
The disadvantage of the described process is that the active agent can only be dispersed in the polymer matrix in limited amounts and in order to insure its retention in the matrix its handling and working is difficult. Despite observed precautions, the active agent, before actual use of the active agent treated matrix already to a considerable extent has separated out of the polymer.
There, therefore still exists a need for improved units which contain at least one active agent which can be released into the environment in a controlled manner over a prolonged period of time.